Prognostic stratification of renal cell carcinoma using a pathological triad of microvascular invasion, Fuhrman's grade and tumor size.

Out of all the patients of RCC presenting to the authors’ institution over a span of 15 years, those that underwent radical or partial nephrectomy were included in the study whereas those with metastatic disease at the time of diagnosis were excluded. The records of 230 patients who met the inclusion criterion were analyzed with respect to variables like clinical presentation, histological type, Fuhrman grade, tumor size, lymph node involvement and presence of microvascular invasion (MVI). The correlation of each of these variables with survival rates and recurrence was estimated. The overall cancer-specific mortality rate was 13% (31 of 230) and recurrence rate was 17% (39 of 230) on a median follow-up of 48 months (range three to 140). On multivariate analysis, microvascular tumor invasion, tumor grade and tumor size had the most significant correlation with disease-free survival and recurrence.


SummARy
In order to analyze the prognostic value of various clinico-pathological variables, the authors conducted a retrospective study on patients undergoing surgery for localized renal cell carcinoma (RCC).
Out of all the patients of RCC presenting to the authors' institution over a span of 15 years, those that underwent radical or partial nephrectomy were included in the study whereas those with metastatic disease at the time of diagnosis were excluded. The records of 230 patients who met the inclusion criterion were analyzed with respect to variables like clinical presentation, histological type, Fuhrman grade, tumor size, lymph node involvement and presence of microvascular invasion (MVI). The correlation of each of these variables with survival rates and recurrence was estimated. The overall cancer-specific mortality rate was 13% (31 of 230) and recurrence rate was 17% (39 of 230) on a median follow-up of 48 months (range three to 140). On multivariate analysis, microvascular tumor invasion, tumor grade and tumor size had the most significant correlation with disease-free survival and recurrence.
Using these three independent variables, survival probabilities were stratified into low risk (Fuhrman's Grade 1 or 2, diameter 7 cm or less, MVI absent); high risk (Fuhrman's Grade 3 or 4, diameter greater than 7 cm, MVI present) and intermediate risk (1 or 2 highrisk variables). On Kaplan Meier analysis, these three categories had a disease-free survival rates of 94.7%, 56.8% and 13.1% and cancer-specific survival rates of 94.7%, 61.7% and 32.0% respectively.

CommenTS
Recent understanding of cellular processes governing tumor biology has led to the development of various novel treatment options in RCC. Sunitinib, Sorafenib and Axitinib are kinase inhibitors that inhibit the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and c-kit receptor tyrosine kinases. Bevacizumab is a monoclonal antibody that is directed against VEGF. Temsirolimus inhibits the mammalian target of rapamycin. [1] Survival benefits reported with Sorafenib and Sunitinib has led to their approval for advanced RCC by regulatory authorities. [2] With the advent of these promising drugs, prognostication of patients with renal cell carcinoma has gained immense importance since viable options for further treatment can be explored in high-risk groups. Furthermore, after undergoing nephrectomy, patients are very anxious to know the further course of their disease.
Until the recent past, tumor stage was considered to be the most important prognostic factor. Other variables like clinical manifestation, tumor size, Fuhrman's grade, lymph node involvement and tumor necrosis have also been seen to have significant correlation in various studies. Microvascular invasion (MVI) is rapidly attaining a distinct position in oncology. It is defined as the presence of cancer cells inside intratumor microvessels. Its role as a prognostic factor has already been established in penile cancers and it plays an important role in algorithms, which decide the need for lymph node dissection following penectomy.
Its impact on prognosis of RCC is an emerging topic of interest. In a recent study, the five-year survival after surgery for low-grade RCC was estimated to be 45% and 90% in the presence and absence of MVI respectively. [3] Microvascular invasion is definitely evolving as one of the most important independent prognostic parameters in RCC. However, it is for the first time in the present study that an attempt has been made to combine MVI with tumor grade and size to stratify RCC patients into different risk categories.
The median follow-up period in this study was 48 months (range three to 140). Studies with a longer follow-up would be required to authenticate the predictive value of these risk categories. Including this risk stratification in the armamentarium of prognostic tools would help physicians in counseling patients about the severity of their disease and also in enrolling patients for novel therapies.

ReFeRenCeS SummARy
This study was a multicenter, randomized clinical trial comparing pubovaginal sling using autologous rectus fascia and Burch colposuspension among women with stress urinary incontinence. Women were eligible for the study if they had predominant symptoms of stress urinary incontinence, a positive stress test and urethral hypermobility. The primary outcomes were success in terms of overall urinary incontinence measures which required a negative pad test, no urinary incontinence (as recorded in a three-day diary), a negative cough and Valsalva stress test, no self-reported symptoms and no retreatment for the condition. Postoperative urge incontinence, voiding dysfunction and other adverse events were also assessed. Six hundred and fifty-five women were randomly assigned to two study groups to undergo either the sling procedure (326) or Burch colposuspension (329). Five hundred and twenty women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both overall category of success (47% vs. 38%, P = 0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty in voiding and postoperative urge incontinence. Hence the authors have concluded that autologous fascial sling results in a higher rate of successful treatment of stress incontinence than Burch colposuspension but the morbidity with the sling was higher than with colposuspension.

CommenTS
This study [1] compares the outcome following autologous fascial sling versus Burch colposuspension for stress urinary incontinence. Incontinence rates as high as 69% have been reported in the community. [2] The ideal manner with which to report the outcomes of surgical interventions-or for that manner any intervention for any disease or symptom state-remains unsettled. This issue is particular for all trials; however, for a study affecting quality of life, this is more significant. [3] Even in multicentric trials, interpretation of results may be difficult if the selection criteria, measures of efficacy and frequency of follow-up are not adequate. [4] This well-conducted prospective, randomized multicentric trial compared autologous fascial sling with Burch colposuspension for stress incontinence. The subjects were randomized just prior to surgery leaving out room for bias on the part of the surgeon. The selection criteria were fairly uniform. The two procedures were standardized and the two main outcomes were composite measures of success in terms of overall continence and stress incontinence specifically. Both Burch colposuspension and the sling procedure have been reported to have success rates of 70-80% at five to eight years. [5,6] In this study, though the initial cure rates were high, there was a decline in the cure rates over